Plasma parathyroid hormone (PTH) was measured in adult, age-matched, intact normal mice and Hyp male mice (n = 11/genotype). Hyp mice are an animal model for the human disease X-linked hypophosphatemia. A RIA was used which detects intact and carboxyl-terminal fragments of PTH. Hyp mice were found to have significantly higher plasma PTH levels (0.21 ± 0.03 ng bovine PTH eq/ml) than normal mice (0.04 ± 0.03 ng/ml; P < 0.01). This hyperparathyroidism in the slightly hypocalcemic, osteomalacic Hyp mice may be the result of skeletal resistance to endogenous PTH and may contribute to their characteristically elevated renal excretion of phosphate and urinary cAMP.